Sphingolipid is obtained by biosynthesis starting from a condensation reaction between L-serine and an acyl CoA such as palmitoyl-CoA. The basic structure of a sphingolipid, i.e., a sphingoid base, is mainly synthesized as a molecule having a chain length of 18 carbon atoms and known as e.g., sphingosine, phytosphingosine, dihydrosphingosine (sphinganine) and 6-hydroxy sphingosine. Each of these sphingoid bases is bound to a fatty acid via an amide bond to synthesize a ceramide.
Sphingolipid has many physiological functions. Particularly ceramide and a sphingoid base, which are involved in skin-moisturizing function and skin barrier function, suppress moisture evaporation from the skin and play a role in protecting human bodies from various external stimuli. Phytosphingosine is reported to have a growth inhibitory effect against Staphyrococcus aureus, Streptococcus pyogenes, Micrococcus luteus, Propionibacterium acnes, Candida albicans and Trichophyton mentagrophytes (Non Patent Literatures 1 and 2). In particular, the antibacterial effect of phytosphingosine on Propionibacterium acnes is known to be higher than that of erythromycin, which is one of macrolide antibiotics (Non Patent Literature 3).
It is known that supply of a ceramide or a sphingoid base by external application shows an effect of improving skin properties. Furthermore, it has been confirmed that when phytosphingosine and tetraacetylphytosphingosine, which is an acetylated phytosphingosine, are applied to the skin, they are permeated into the skin and converted into a ceramide (Patent Literature 1). Accordingly, external application of ceramide, a sphingoid base or acetylated phytosphingosine is expected to have an improving effect on skin property and a growth inhibitory effect against microorganisms responsible for infection.
Recently, a technique for specifically analyzing the ceramide composition of skin has been established and it has been found that there are 12 classes (340 or more species) of ceramide molecular species formed by combinations of a fatty acid and a sphingoid base (Non Patent Literature 4). For example, as ceramide NP formed by a combination of a saturated fatty acid and a phytosphingosine, a combination of a fatty acid having a chain length of from 23 to 30 carbon atoms and a phytosphingosine having a chain length of from 16 to 26 carbon atoms is found and a molecule having a chain length of from 40 to 52 carbon atoms in total of the fatty acid and phytosphingosine is known to be present. As ceramide NS formed by a combination of a saturated fatty acid and a sphingosine, a combination of a fatty acid having a chain length of from 16 to 30 carbon atoms and a sphingosine having a chain length of from 16 to 26 carbon atoms is found and a molecule having a chain length of from 40 to 54 carbon atoms in total of the fatty acid and a sphingosine is known to be present (Non Patent Literature 4). It is known that healthy skin contains a large amount of long-chain ceramide; whereas the content of ceramide is lowered in rough skin and additionally the amount of short-chain ceramide is increased (Non Patent Literature 5). From this, usefulness of a long-chain ceramide or a sphingoid base is expected.
However, currently commercially available ceramide, a sphingoid base and acetylated phytosphingosine are extremely expensive, e.g., several tens to several hundreds of thousands of yen per kg. In addition, the length of a carbon chain of them is limited. For example, for ceramide NP and ceramide NS, molecules having 34, 36 or 40 carbon atoms are only available; and for phytosphingosine and sphingosine, molecules having 18 carbon atoms are only available.
Since it is difficult to separate and purify animal- or plant-derived sphingolipids, a method for producing a sphingolipid by yeast fermentation has been recently developed as a method for producing a ceramide and a sphingoid base. Candidate yeast strains include Pichia ciferrii; at present Wickerhamomyces ciferrii, Candida utilis and Saccharomyces cerevisiae, and a method for obtaining tetraacetylphytosphingosine using Wickerhamomyces ciferrii, which secrets tetraacetylphytosphingosine out of the yeast cells, has been positively developed (Patent Literature 6). The length of carbon chain of acetylated phytosphingosine produced by this method is mostly 18 carbon atoms. Acetylated phytosphingosine is deacetylated and used as phytosphingosine, or bound to a fatty acid via an amide bond through a chemical synthesis and used as a ceramide.
It has been elucidated by in-vitro analysis of biosynthesis pathway that the rate-limiting steps of tetraacetylphytosphingosine synthesis in Wickerhamomyces ciferrii are a condensation reaction between serine and palmitoyl-CoA and an acetylation reaction of phytosphingosine. In addition, two acetylation enzymes for phytosphingosine, SLI1 and ATF2, are found (Non Patent Literature 7). Among them, SLI1 produces triacetylphytosphingosine when it is expressed in Saccharomyces cerevisiae (Non Patent Literature 6). From this, it is considered that SLI1 is involved in acetylation of any three sites of 3 hydroxy groups and a single amino group of phytosphingosine.
In the meantime, a microorganism of the genus Starmerella, for example, Starmerella bombicola (old scientific name: Candida bombicola), can produce a significant amount of sugar lipid serving as a biosurfactant out of the cells and is known as a microorganism having high lipid availability (Non Patent Literature 8). However, little is known about whether the microorganism produces a ceramide or a sphingolipid.    [Patent Literature 1] U.S. Pat. No. 5,578,641    [Patent Literature 2] JP-A-9-504434    [Non Patent Literature 1] Bibel D. J. et. al., J. Invest. Dermatol., 98, 269, (1992)    [Non Patent Literature 2] Bibel D. J. et. al., Clin. Exper. Dermatol., 20, 395, (1995)    [Non Patent Literature 3] Park C. et. al., Fragrance journal, 10, 84, (1999)    [Non Patent Literature 4] Masukawa Y. et. al., J. Lipid Res., 49, 1466, (2008)    [Non Patent Literature 5] Ishikawa J. et. al., J. Invest. Dermatol., 130, 2511, (2010)    [Non Patent Literature 6] Veld, F. et. al., Appi. Microbiol, Biotechnol., 97, 8537, (2013)    [Non Patent Literature 7] Barenholz, Y. et. al., Biochim. Biophys. Acta, 306, 341, (1973)    [Non Patent Literature 8] Udo R. et. Al., Biotechnology Letters, 18 (2), 149, (1996)